The Real-World Outcomes of Ponatinib in 724 Patients with CML and Ph + ALL : A Post-Marketing Surveillance Study with a Special Interest in Arterial Occlusive Events in Japan

Introduction Ponatinib inhibits the BCR::ABL1 kinase, including a variant with threonine-to-isoleucine at position 315 (T315I) (Cortes et al. N Eng J Med. 2013; 369:1783-96); however, it has been reported that ponatinib is associated with a higher risk of major arterial events than other TKIs among patients with CML, those with a resistance/intolerance (r/i) to prior TKIs, and with patients with relapsed/refractory (r/r) Ph + ALL. ( Leuk Lymphoma. 2016; 57(6):1300-10.) Owing to the low prevalence of this disease (Ning et al. Exp Hematol Oncol 2020; 9 (29)), SEER Cancer Statistics Review 1975-2018. National Cancer Institute 2021, Ching-Hong et al. N Engl J Med 2004; 350:1535-48), the amount of data concerning patients treated with ponatinib is limited, indicating that the safety and efficacy of ponatinib require further evaluation. Therefore, we conducted a post-marketing surveillance (PMS) study to assess the safety and efficacy of ponatinib, focusing on arterial occlusive events (AOEs), to optimize its use in clinical practice in Japan. Methods This PMS study investigated the safety and efficacy of ponatinib (ICLUSIG ®, Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan) in patients with r/i CML who have been treated with TKIs and patients with r/r Ph + ALL. We collected clinical data from all patients in Japan who started ponatinib administration between November 21, 2016, and June 30, 2018. The observation period was two years (or until the end of ponatinib administration). AEs and ADRs were classified using the Medical Dictionary of Regulatory Affairs (MedDRA) version 25.0. Surveillance was conducted in accordance with the Japanese Ministerial Ordinance on Good Post-Marketing Study Practice for Drugs. Results A total of 807 patients were enrolled from 334 facilities. Safety analysis was conducted for all 724 patients; 421 (58.1%) participants were males with a sample median age of 62.0 years. The median (range) follow-up duration was 258.0 (1-1,436) days for the overall population, 729.5 (7-1,436) days for patients with CML-CP, and 168.0 (1-1,254) days for patients with Ph + ALL. As for safety data, adverse reactions (ADRs) were observed in 58.29% (422/724) of participants. The most common ADRs included platelet count decreases (8.15% - 59/724), hypertension (7.73% - 56/724), rash (5.56% - 41/724), decreased neutrophil count (4.83% - 35/724), and abnormal hepatic function (4.28% - 31/724). The most common serious ADR was a 2.49% (18/724) decrease in the pla